Many people now know about the dangers of DPT shots in babies. and they are
rejecting those particular shots. Yet, they still accept other vaccines for
their children. So for those trusting souls, here is the latest evidence on
the dangers of the German measles vaccine.

A study of 200 patients with Epstein-Barr Virus (often called Yuppie
disease) is scheduled for publication this spring in the journal Medical
Hypothesis. In an advance report in the San Diego Tribune (September 30.
1987). the study’s researchers have linked EBV syndrome to exposure to the
weakened. but live, rubella virus found in the vaccine. Given to young
children, the vaccine can linger in their systems for years and can be
passed to adults through casual contact.

Biomedical researcher Allen D. Allen of Algorithms. Inc. of Northridge.
California, blames EBV syndrome on Merck Sharp and Dohme’s Biavax and
Meruvax vaccines which were introduced in the late 1970’s. Allen says. ‘I
can say all this attention to the (Epstein-Barr) syndrome. the public
awareness. started in the early 1980’s. right after these vaccines came out.
Young adults. the ones most likely to be in contact with young children, are
the primary targets. It’s too much of a coincidence to ignore."

In a similar study. Dr. Hugh Fudenberg
http://members.aol.com/nitrf,
professor of immunology at the Medical University in Charleston. South
Carolina. found the same linkage in 24 patients.

Doctors have long
struggled to find the cause of lupus. a chronic disease of the immune system
that mainly affects women. Now , new research on children shows that it may
be linked to Epstein- Barr, the virus that causes mononucleosis. In a recent
study, researchers found that 99 percent of lupus patients had been exposed
to the Epstein-Barr virus compared to 70 percent of those without the
disease. " It may be that lupus patients are extremely susceptible to
Epstein-Barr." or that the virus is a precursor to the disease, explains
researcher John Harley, M.D. at the University of Oklahoma Medical Research
Foundation, University of Oklahoma Health Sciences Center in Oklahoma City.
Doctors hope this new discovery will aid in their efforts to find a cure for
lupus.

Steve Salvatore, D.O.,
CNN Medical

Multiple Sclerosis May be Linked to
Infection

Despite decades of research, the cause of multiple sclerosis remains
unknown. In the past it was suggested that the disease might be
immunological, though more recently it is thought that it could be a genetic
disease.

Scientists have also focused on
chlamydia pneumonia and the Epstein-Barr virus as it was found that
patients with multiple sclerosis had an increase in respiratory infections
before the onset of the disease. However, it is unknown whether the
Epstein-Barr virus plays a specific role in multiple sclerosis or is an
indication of an immune system response in patients with the disease.

A vascular theory for multiple sclerosis has also been discussed, along with
dietary therapies, which have a vascular defect as part of the rationale. It
has been suggested that vascular changes may precede the inflammation and
demyelination in a multiple sclerosis plaque. Those that advocate the
infection theory believe that an infection could be the initial event that
brings on this process.

In terms of the genetic factor of
the disease, research has shown that siblings and fraternal twins have a
greater risk, by about two to five percent, than the general population. In
identical twins, this risk is about 30 percent higher. While this seems to
support the genetic proponent, the question has been raised of why all
genetically disposed individuals do not get the disease. To explain this,
researchers say that multiple sclerosis may be determined by multiple genes
and an environmental factor, possibly infection.

One common theory holds that genetics, viral infections, and immune
reactions all play a role in multiple sclerosis.

AAN: Child-Onset Multiple Sclerosis More Likely to Have epstein-barr virus
Antibodies than Controls

By Paula Moyer

HONOLULU, HI -- April 8, 2003 -- Children who have multiple sclerosis (MS)
are more likely than healthy children to be seropositive for Epstein-Barr
virus (EBV), according to researchers. "EBV seropositive status is
significantly associated with paediatric MS," said Brenda L. Banwell, MD,
the director of the paediatric MS unit at the Hospital for Sick Children in
Toronto, Ontario, Canada. Because of EBV's lifelong effects on B cell
proliferation and T cell surveillance, it "may play a pivotal role in the
autoimmune milieu that fosters MS." She presented findings of her team's
study here at the 55th Annual Meeting of the American Academy of Neurology.

Dr. Banwell and her colleagues wanted to compare the seropositive status for
common viruses in patients with paediatric multiple sclerosis and in
controls. Their rationale was that several investigators have postulated
that infection by a common virus such as EBV in a genetically pre-disposed
host may be a pathobiological mechanism for MS.

The literature has also shown that adults with MS have higher seropositivity
for EBV than controls do and that EBV infection has been associated with
other demyelinating disorders, including optic neuritis and central nervous
system demyelination. Further, research has shown that infection with acute
mononucleosis in adulthood increases the risk of MS several times over.

One complication to testing the theory in adults is that EBV seropositivity
is nearly universal by adulthood, with 90% of adults having EBV antibodies.
Therefore, comparative analysis is limited between adult MS patients and
controls. It was necessary to study paediatric patients, instead, she said,
since fewer children are EBV-positive than are adults. Dr. Banwell and her
colleagues theorised that MS patients might be EBV-positive before their
healthy peers have had exposure to the virus.

The investigative team obtained serum samples from 25 children with
clinically diagnosed MS and 75 age-matched controls, who were matched at a
3:1 ratio for birth year for each MS patient. Control samples were obtained
from previously healthy children for whom serology had been drawn previously
due to acute symptoms of abdominal pain, pharyngitis, or rash.

All 100 samples were analysed for EBV capsid antigen (EBV-VCA), EBV nuclear
antigen (EBV-EBNA), and EBV early antigen (EBV-EA). The researchers also
analysed all 25 MS samples and a random sampling of 15 of the age-matched
control samples for parvovirus B19 (parvo B19), cytomegalovirus (CMV), and varicella zoster (VZV). The investigators coded and analysed all samples in
a uniform manner by the ELISA technique (as per manufacturer s
instructions). The study virologist then interpreted results in a blinded
manner.

Dr. Bandwell and her co-investigators found that EBV seropositivity differed
markedly between paediatric MS patients and age-matched controls. Although
89% of paediatric MS patients were positive for EBV-VCA and EBV-EBNA, which
indicated a temporally remote infection, 31% of controls had such infections
(p 0.0004). Among the MS patients, 3 (12%) were negative for all three EBV
antigens.

The investigators found no statistical significance regarding seropositivity
for the other viruses between MS patients and controls. For parvovirus B19
the infection rates were 49% and 64%, respectively (p=NS). For CMV the rates
were 42% and 64%, respectively (p=NS). For VZV those rates were 88% and 92%,
respectively (p=NS).

This discrepancy in EBV seropositivity between paediatric MS patients and
controls is "considerably more robust" than similar studies of EBV in adult
MS patients, Dr. Banwell said. The finding demonstrates the advantage of
comparative studies in which healthy subjects are relatively naïve to common
infections.

Because exposure to other common viruses does not differ between paediatric
MS patients and controls, the findings suggest that the association between
MS and EBV may be specific, Dr. Banwell said.

The study was supported by a grant from The Hospital for Sick Children
Foundation.

The Epstein-Barr virus (EBV) would win the prize for most versatile virus if
Academy Awards were given to microbes. Both acute and chronic infections
produce a wide variety of symptoms from minor illness to fulminant
malignancy. The repertoire of the virus is extended to chronic neurologic
disease in this brief report by investigators at the Walter Reed Army
Institute of Research and collaborators at the Harvard School of Public
Health and Virolab Inc. (Berkeley, California). The investigators showed a
relationship between titer of serum IgG antibodies to viral capsid antigen
(VCA) or EBV nuclear antigen (EBNA) complex and subsequent diagnosis of
multiple sclerosis (MS). The relative risk is plausible, graded, and
substantial. Although not proving causation, this study suggests the
possibility of new ideas to prevent and treat multiple sclerosis.

The investigators used the extensive US Defense Department serum bank, which
contains samples from more than 3 million persons collected at entry into
service and approximately every 2 years starting in 1988. They identified
cases of MS (defined as certain or probable on the basis of diagnostic
criteria that included MRI and examination by a neurologist) from records of
the US Army Disability Agency. Cases were each matched to 2 controls by age,
sex, race/ethnicity, and date of blood draw. Samples were subjected to IgG
and IgA antibody tests for VCA, anti-early antigen complex (EA-D and EA-R),
and IgG antibodies against EBNA complex and EBNA-1 and EBNA-2. IgG
antibodies to cytomegalovirus (CMV) were also measured in all cases and
controls. Finally, cases and controls were compared using geometric mean
antibody titers against all of the antigens.

There were 83 cases and 166 controls. All cases and 98% of the controls had
evidence of exposure to EBV at entry into the service. Mean age of onset of
MS was 27 years, with diagnosis considered certain in 64% and probable in
36%. A mean of 4 years elapsed between first blood draw and onset of
illness. The baseline geometric VCA and EBNA complex IgG antibody levels
were significantly higher in cases than in controls. Additionally, the risk
of MS rose significantly as the titer increased. The relative MS risk of
subjects with highest compared to lowest VCA and EBNA IgG titers were 19.7
and 33.9, respectively. There was no association of risk to CMV antibodies,
race, age, or sex. Using simultaneous regression analysis, only high EBNA
complex antibody and EBNA-1 antibody correlated to risk. Interestingly, the
VCA and EBNA antibody levels remained stable across time, even after the
onset of disease.

The investigators state that the pattern of high VCA, high EBNA seen in the
patients with MS suggests recent EBV infection or reactivation with vigorous
cellular immune response. They also suggest that this pattern has been
associated with greater risk of Hodgkin's disease and nasopharyngeal cancer.
Could the high titer represent continued viral replication in the central
nervous system? With new anti-herpes medications potentially achieving
sufficient activity against EBV in the central nervous system, it might be
time to see whether anti-EBV therapy is beneficial for this dreaded
disease. On the other hand, it increasingly looks like a vaccine against
EBV given early in childhood might be a good thing.

Here is my thought and it's a radical
one......Don't inject people with it in the first place! Or another
thought....take EBV out of the polio vaccine to begin with!

Epstein-Barr Virus
Linked to Multiple Sclerosis

Laurie Barclay, MD

March 25, 2003 — Epstein-Barr virus (EBV) is associated with increased risk
of multiple sclerosis (MS), according to the results of a large, nested,
case-control study published in the March 26 issue of The Journal of the
American Medical Association.

"The baseline geometric mean serum antibody titers to EBV were consistently
higher among individuals who later developed MS than among their matched
controls," write Lynn I. Levin, PhD, MPH, from the U.S. Army Physical
Disability Agency in Washington, D.C., and colleagues. "Similarly strong
positive associations between EBV antibodies and risk of MS were already
present in samples collected five or more years before MS onset."

Using the Department of Defense Serum Repository of blood samples collected
between 1988 and 2000 from more than 3 million U.S. military personnel, the
investigators identified 83 individuals granted temporary or permanent
disability because of MS. Two controls for each of these cases were matched
by age, sex, race, ethnicity, and dates of blood sample collection. The mean
length of time between blood collection and onset of MS was four years.

Samples collected five years or more before MS onset also showed strong
positive associations between EBV antibodies and risk of MS. No relationship
was detected between cytomegalovirus antibodies and risk of MS.

According to the authors, these findings suggest that "the increased
antibody response to EBV occurs early in relation to the pathological
process that leads to demyelination and clinical disease," and that "there
is a long lag time between infection with EBV and occurrence of MS.... These
results support a role for EBV in the etiology of MS."

Soderlin and coworkers in this publication and previously[1] report an
epidemiologic study of infections preceding arthritis in Southern Sweden.
Among a population of 132,000 adults living in the study region, 71 were
identified as developing arthritis during the 1999-2000 time period. These
patients were systematically screened for infections caused by Salmonella
typhimurium and Salmonella enteritidis, Yersinia enterocolitica,
Campylobacter jejuni, Borrelia burgdorferi, Chlamydia trachomatis, Chlamydia
pneumoniae, and parvovirus B19. Twenty-seven (38%) patients had reactive
arthritis (ReA), 17 (24%) undifferentiated arthritis, 15 (21%) rheumatoid
arthritis (RA), 4 (6%) psoriatic arthritis, and the rest (11%) other
diagnoses. Forty-five percent had evidence of infection recently preceding
the arthritis, as indicated by laboratory tests and/or disease history. C
jejuni dominated the ReA group. Recent C trachomatis, B burgdorferi, C
pneumoniae, and parvovirus B19 infections occurred infrequently. This study
is important to rheumatologists because environmental factors have long been
considered to have a causative role in reactive arthritis, but a long search
for infectious agents in RA has not turned up any clear single candidate for
RA. However, the dramatic success of TNF inhibitors in RA has led to renewed
interest in the "innate" immune system (discussed below) , which has a major
role in response to infectious agents.

The latest study by Soderlin and colleagues extends prior studies looking
for specific infective triggers for RA based on serological methods to
detect prior exposure, culture or molecular methods to detect the organism
or its genetic material in blood or synovial tissue.[2] However, the study
by Soderlin and coworkers has limitations that the author and the
accompanying editorial point out.[1] In particular, the study examines
subjects with established disease. The authors note that results of their
study need to be treated with caution. First, their study lacks appropriate
controls. Second, the disease itself or its treatment might increase the
likelihood of infection. Third, the detection of an organism in synovium
(even in viable, replicating form) is not necessarily indicative of an
active role in pathogenesis: there is evidence that synovial tissue may
nonspecifically trap bacteria and viruses,[3,4] and others may enter the
inflamed synovium because they are parasitic residents of cells entering the
joint (such as Epstein-Barr virus in B cells).[2] Nevertheless, the study by
Soderlin and coworkers provides an interesting link between studies on
pathogenesis and current trends in therapy of RA.

Although genetic factors are important in the development of RA, not all
those who are genetically susceptible develop the disease. Twin studies in
the United Kingdom and Australia have shown disease concordance rates in
monozygotic twins of between 15% and 21%.[5,6] Earlier studies also showed
only modest concordance for autoantibody and immunoglobulin production
within twin pairs.[7,8] There is weak evidence, also, of an increased
concordance of RA, rheumatoid factor, and other autoantibodies within spouse
pairs.[9] There is also the intriguing observation that skeletons with
characteristic findings of RA were not detected in Europe before the 1500s,
suggesting that RA may be partly an "infectious" disease that developed as
new gene pools came into contact with new organisms as a result of increased
movement of populations in Europe.[10]

No single specific self-antigen or environmental antigen has been identified
as responsible for inducing or perpetuating RA. Many investigators believe
that RA develops in 2 stages in which an initial response induced by a
foreign antigen (most likely an infectious organism) subsequently develops
into a self-sustaining autoimmune process. Because the specific genetic and
environmental agents are not known, rheumatologists increasingly look at
pathogenesis in terms of sites for therapeutic action. One class of drugs is
similar to those developed in assays for transplant rejection, namely HLA-D
linked presentation of antigens to T cells (ie, hydroxychloroquine,
cyclosporine, leflunomide, mycophenolic acid, and probably methotrexate).
These drugs target the "acquired" immune system that is regulated by
activated T cells. Although these drugs have been effective, the dramatic
(and perhaps unexpected) success of TNF inhibitors has focused attention on
the "innate" immune response, which is parallel but distinct from the
"acquired" immune response.[11] Therapies originally developed for therapy
of septic shock (ie, targeting the release of endotoxin by the innate immune
system) later proved to be dramatically effective in RA.[12,13] Although the
innate and acquired immune systems have distinct characteristics they are
also interactive through a series of cytokines and second signals, which are
designed to help the immune system to distinguish self from nonself.[14,15]

Recognition of pathogens by the innate immune system is mediated by a set of
germline-encoded receptors that are referred to as pattern-recognition
receptors (PRRs).[11] These receptors recognize conserved molecular patterns
(pathogen-associated molecular patterns), which are shared by large groups
of microorganisms.[12] Toll-like receptors (TLRs) function as the PRRs in
mammals and play an essential role in the recognition of microbial
components.[13] The TLRs may also recognize endogenous ligands induced
during the inflammatory response.[16]

TLRs are type I transmembrane proteins that contain leucine-rich repeats in
the extracellular domain and a cytoplasmic Toll/interleukin-1 (IL-1)
receptor homology domain.[17] This receptor family has been phylogenetically
conserved, from insects through vertebrates.[11] Signaling through TLR is a
multistep process. Initially, TLRs interact with the MyD88 adapter molecule,
initiating a signaling cascade that involves members of the IL-1
receptor-associated kinase family and TNF receptor-associated factor 6, the
activation of downstream kinases, and the translocation of nuclear factor B
(NF-B) from the cytoplasm to the nucleus.[18] NF-B up-regulates the
transcription of genes encoding cytokines, chemokines, and other
immunomodulatory factors.[12,13]

The TLRs recognize determinants that have been conserved at high frequency
in prokaryotes but are rare in eukaryotes. Ten TLR family members have been
identified in mammals.[18] For example, TLR-2 mediates recognition of
bacterial lipoproteins and peptidoglycans, TLR-3 binds to viral
double-stranded RNA, TLR-4 recognizes the bacterial cell membrane components
lipopolysaccharide and lipoteichoic acid, TLR-5 recognizes flagellin, and
TLR-9 interacts with unmethylated CpG motifs present in bacterial DNA. This
pattern of innate immune response has been shown to improve the host's
ability to limit the proliferation and spread of infectious pathogens in the
period before development of acquired antigen-specific
immunity.[11,14,15,19]

In summary, as rheumatologists, we use therapies for arthritis that were
originally detected in screens for transplant rejection based on the
cyclosporin A model (namely the HLA-DR-linked T-cell activation that defined
the acquired immune response). More recently, we have used therapies
originally designed for treatment of septic shock due to endotoxin, a
process that has led to recognition of Toll receptors and the innate immune
system. This study by Soderlin and colleagues points out that arthritis
patients are frequently challenged by environmental infections just before
onset of their arthritis and reminds us that a mistake in distinguishing
self from nonself may have the pathogenetic consequences of arthritis.

[By Jennifer Warner. For more information on how it may apply to
autism, reference the NIDS site and Center for Complex Infectious Disease
www.ccid.org. Thanks to Tashia Berman.]
http://sar.c.tclk.net/maabn17aaZ41aa4JiD8b/rs81766&src=webmd < - - Address ends here.

Certain viral infections may increase the likelihood of mental decline
and dementia, especially among older adults with heart disease. A new
study shows that elderly people with evidence of infection with three common
viruses -- viruses that cause cold sores, genital herpes, and a mono-like
illness -- were more than twice as likely to suffer from dementia.
Researchers say the study adds new evidence to the theory that inflammation,
which is part of the body's natural response to infection, plays an
important role in the development of several health problems, such as heart
disease, stroke, and dementia.

Viruses May Trigger Dementia “Inflammation has been implicated in
dementia, and viral infections could be a triggering factor,” says
researcher Timo E. Strandberg, MD, PhD, of the University of Helsinki in
Finland, in a news release. “Our findings should be tested in other studies,
but if these viruses are involved, there are existing therapies such as
vaccination and antiviral drugs that could be used to prevent or treat
dementia.”

In the study, which appears in Stroke: Journal of the American Heart
Association, researchers tested 383 elderly men and women with heart disease
for the antibodies that are produced in response to infection with three
common viruses: herpes simplex 1 (HSV1), herpes simplex type 2 (HSV2) and
cytomegalovirus (CMV), and followed them for 12 months. HSV1 causes
cold sores, and HSV2 causes genital herpes. CMV is a virus that infects
between 50% to 85% of American adults by age 40, but it causes few symptoms
and no long-term health problems in most people. The mental function
of the participants was also assessed at the beginning and end of the study.

After testing for the viruses multiple times, researchers found that
up to 60% of the participants tested positive for one or more or the
viruses. And the more viral exposure, the higher the risk of dementia.
Those who had evidence of infection with all three viruses were 2.5 times
more likely to have mental impairment than those with antibodies for less
than three of the viruses.

Dementia was found in about 5% of people who were infected with one or
none of the viruses, but those numbers grew dramatically with additional
infections. Sixteen percent of those infected with two viruses had dementia
and 27% of those exposed to all three had dementia.

The researchers also looked at whether infection with two common
bacteria was related to dementia risk but found no association between
bacterial infections and mental decline. Because all of the
participants also had heart disease, researchers say further studies should
examine whether similar results are found in otherwise healthy individuals.
SOURCES: Stroke: Journal of the American Heart Association, Aug. 15,
2003. News release, American Heart Association.
* * *

Epstein-Barr Virus-Associated Lymphadenitis: The Differential Diagnosis
of
Diffuse Paracortical Lymphoid Hyperplasia. Pathology Case Reviews. 9(5):192-198, September/October 2004. Abbondanzo, Susan L. MD
Abstract:
The diagnosis of infectious mononucleosis associated with Epstein-Barrvirus
(EBV) is usually based on a constellation of clinical signs and symptoms
and a correlation with laboratory findings. In classic cases,there is a
triad that includes sore throat, fever, and cervical (orgeneralized)
lymphadenopathy. In some cases, however, the only presenting
features may be fever and malaise, with or without lymphadenopathy.
Important laboratory findings include leukocytosis with circulating
atypical lymphocytes, a positive Monospot test, and characteristic
serologic antibodies that are subsequently produced as an immunologic
response to the virus. A lymph node biopsy is usually not necessary to
make the diagnosis of EBV-related infectious mononucleosis and is
actually discouraged because the histologic features may be worrisome and
may mimic a malignant lymphoma. In rare cases, however, especially
those with atypical clinical presentations,an excisional lymph node
biopsy is performed as part of the routine clinical workup. It is
important to be familiar with the characteristic histologic features,
including diffuse paracortical lymphoid hyperplasia, and to be
aware of the differential diagnosis that includes reactive entities as
well as malignant lymphomas. Important benign entities that
characteristically show diffuse paracortical lymphoid hyperplasia include
other viral lymphadenitides such as herpes simplex, cytomegalovirus, postvaccinial and measles lymphadenitis, and drug-related
lymphadenopathy, especially Dilantin. Malignant neoplasms,such as diffuse
large B-cell-, Hodgkin-, and CD30-positive anaplasticlarge-cell lymphoma,
are also in the differential diagnosis of EBV-associated lymphadenitis.(C)
2004 Lippincott Williams & Wilkins, Inc.

Context The "hygiene hypothesis" has implicated sibship as a marker of
infection load during early life and suggests that exposure or reexposure
to infections can influence the developing immune system. Viral infection
has also been implicated in the pathogenesis of multiple sclerosis (MS).
Objectives To evaluate whether exposure to infant siblings in early life
is associated with the risk of MS, and to explore the possible mechanism
for any apparent protective effect, including altered Epstein-Barr virus
(EBV) infection patterns.

Design, Setting, and Patients Population-based case-control study in
Tasmania, Australia, from 1999 to 2001 based on 136 cases of magnetic
resonance imaging-confirmed MS and 272 community controls, matched on sex
and year of birth. Main Outcome Measure Risk of MS by duration of
contact with younger siblings aged less than 2 years in the first 6 years
of life.

Results Increasing duration of contact with a younger sibling aged less
than 2 years in the first 6 years of life was associated with reduced MS
risk (adjusted odds ratios [AORs]: <1 infant-year, 1.00 [reference]; 1 to
<3 infant-years, 0.57 [95% confidence interval {CI}, 0.33-0.98]; 3 to <5
infant-years, 0.40 [95% CI, 0.19-0.92]; 5 infant-years, 0.12 [95% CI,
0.02-0.88]; test for trend, P = .002). A history of exposure to infant
siblings was associated with a reduced IgG response to EBV among
controls.
Controls with at least 1 infant-year contact had a reduced risk of
infectious mononucleosis and a reduced risk of very high composite EBV
IgG titers (AOR, 0.33; 95% CI, 0.11-0.98) compared with other
controls. The inverse association between higher infant contact and MS
was independent of EBV IgG titer.

Conclusion Higher infant sibling exposure in the first 6 years of life
was associated with a reduced risk of MS, possibly by altering childhood
infection patterns and related immune responses.

The origins of autoimmunity in systemic lupus erythematosus (SLE) are
thought to involve both genetic and environmental factors. To identify
environmental agents that could potentially incite autoimmunity, we have
traced the autoantibody response in human SLE back in time, prior to
clinical disease onset, and identified the initial autoantigenic epitope
for some lupus patients positive for antibodies to 60 kDa Ro. This
initial epitope directly cross-reacts with a peptide from the latent
viral protein Epstein-Barr virus nuclear antigen-1 (EBNA-1). Animals
immunized with either the first epitope of 60 kDa Ro or the
cross-reactive EBNA-1epitope progressively develop autoantibodies
binding multiple epitopes of Ro and spliceosomal autoantigens. They
eventually acquire clinical symptoms of lupus such as leukopenia,
thrombocytopenia and renal dysfunction. These data support the hypothesis
that some humoral autoimmunity in human lupus arises through molecular
mimicry between EBNA-1 and lupus autoantigens and provide further
evidence to suspect an etiologic role for Epstein-Barr virus in SLE.

PMID: 15619631 [PubMed - in process]

Lupus and the role of Epstein-Barr virus
08 Apr 2005

Study suggests a common viral infection may increase risk of lupus in
African Americans. Findings also show that genetic variation may affect
the immune response to Epstein-Barr virus in lupus patients.

Almost everyone has been infected with Epstein-Barr virus (EBV), a member
of the herpes family and one of the most common human viruses. Symptoms
of initial infection range from a typically mild childhood illness with a
fever and sore throat to mononucleosis in teenagers or adults. After the
initial infection, the virus settles into the cells of the immune system
called B cells, where it remains for life, mostly dormant, with
occasional bouts of reactivation and replication. Maintaining EBV
infection in a latent or quiet state primarily depends on the power of
another kind of immune cell, known as T cells. T cells play a major role
in keeping the immune system functioning properly. Due to its
interference with immune function and promotion of certain antibodies,
EBV has been implicated in systemic lupus erythematosus (SLE), commonly
referred to as lupus. Lupus is a chronic, potentially debilitating
autoimmune disease that more often affects women and is also more common
in African Americans. Although the specific cause of lupus is not yet
known, both genetic and environmental triggers are likely to be involved.

To determine if there is an association between Epstein-Barr virus and
lupus, researchers in North and South Carolina compared the prevalence of
EBV antibodies in blood samples from lupus patients with those from
healthy controls. Published in the April 2005 issue of Arthritis &
Rheumatism (http://www.interscience.wiley.com/journal/arthritis), the
results of the National Institute of Environmental Health Sciences (NIEHS)
study show a strong association of EBV-IgA antibodies with lupus in
African Americans. In addition, their findings shed new light on
variation in a T-cell response gene that might influence immune
responsiveness to EBV among lupus patients.

Participants in the Carolina Lupus Study included 230 patients recently
diagnosed with lupus. Ranging widely in age, the subjects were 90 percent
women and 60 percent African-American. Matched for age and sex, controls
were recruited from state driver's license registries. 30 percent of the
enrolled controls were African-American, reflecting the racial
distribution of the geographic study area. Blood samples and medical
records were obtained for all participants.

Among both lupus patients and controls, African Americans had a higher
prevalence of EBV-IgG antibodies - the telltale sign of having a history
of EBV infection - than white subjects. However, another antibody,
EBV-IgA, seen with repeat or reactivated EBV infection, was also more
common in African Americans with lupus. EBV-IgA was found in 66 percent
of African-American patients, and calculated at increasing the odds for
lupus by 5 to 6 fold. Among white lupus patients, the EBV-IgA association
was modest, yet increased significantly with age. The association also
appeared stronger in older African Americans than younger patients.

Among lupus patients, both African-American and white, researchers also
observed a genetic variation in CTLA-4, a protein that works on T cells
in regulating immunity, and which significantly increased the risk of
lupus associated with EBV-IgA antibodies. This variation was previously
linked to risk of lupus in younger African Americans in the Carolina
Lupus Study.

"The racial difference in the association between EBV-IgA and SLE is
intriguing, especially since African Americans have a higher risk of SLE,
tend to develop the disease earlier, and often have a more severe course
of disease," notes the study's leading author, Christine G. Parks, Ph.D.,
who performed the study as a post-doctoral fellow at the NIEHS, one of
the National Institutes of Health, in Research Triangle Park, North
Carolina. Dr. Parks is presently employed with the National Institute for
Occupational Safety and Health Sciences in Morgantown, West Virginia.
"One explanation could be that there are more opportunities for
reinfection among African Americans, given the higher population
prevalence of infection and likelihood of encountering and becoming
infected with new viral strains. Alternatively, other factors
independently related to the immune response to EBV and loss of latency
could vary by race, with the same difference being related to the
differential risk of SLE."

Providing solid new serum-based evidence on the link between lupus and
Epstein-Barr virus, this study also calls attention to the need for
continued research into the role of race, age, and genetic variation in
autoimmune diseases.

The National Institute of Environmental Health Sciences is a federal
agency that conducts and funds basic research on the health effects of
exposure to environmental agents.

Canadian researchers have linked the common virus Epstein-Barr with
childhood cases of multiple sclerosis. It's a clue that MS, a
neurological disease, may begin much earlier than thought. With MS, the
immune system attacks the myelin -- the protective covering -- the brain
and spinal cord. The symptoms are varied and can include visual
impairment or blindness, weakness, balance and coordination problems, and
sensitivity to heat. There are an estimated 250 children across Canada
with MS, with about 50 new cases diagnosed each year. The rate of
diagnosis is increasing because of better detection. At the neurology
clinic at Toronto's Hospital for Sick Children, they've seen children as
young as seven months with signs of MS-related damage. But the usual age
of diagnosis for children is between the ages of four and seven.

Dr. Brenda Banwell, a neurologist at the Hospital of Sick Children in
Toronto, was one of the researchers on the study which was published this
week in the Journal of the American Medical Association. Scientists
tested the blood of children with early onset MS, taking samples from
patients in six countries. They tested for the presence of Epstein-Barr
virus (EBV). The study found "Serological evidence for remote EBV
infection was present in 83 per cent of pediatric MS patients compared
with 42 per cent of emergency department and healthy controls."

That result was consistent in children from all the countries involved in
the study.

EBV is a common infection. By age 20 most adults are infected with it.
But it typically causes no symptoms, although it can trigger
mononucleosis, a fever and a sore throat. "Our international study
supports that this is a much broader exposure of children to the virus
and that it may be an important trigger for many if not most children
with MS," Banwell told CTV News. Researchers are now looking at whether
EBV might be triggering MS. They are also considering whether the
presence of EBV might be a signal of another factor, such as a genetic
predisposition or a poorly functioning immune system.

According to the Multiple Sclerosis Society of Canada, Canadians have one
of the highest rates of multiple sclerosis in the world and three new
cases are diagnosed each day.

Researchers map role of Epstein-Barr virus in cancerProtein in virus
immortalizes cells, allows them to keep proliferating

March 31, 2005
by Janet Wong (about) (email)

Researchers at the University of Toronto have mapped the molecular
details that show how a viral protein coded in the Epstein-Barr virus
immortalizes cells and causes them to continuously grow, thereby
predisposing people to certain types of cancer.

“Epstein-Barr virus (EBV) is one of the most common human viruses in the
world and is strongly linked to certain b-cell cancers like Burkitt’s
lymphoma as well as the epithelial cell cancer, nasopharyngeal carcinoma.
EBNA1 is a protein coded in the Epstein-Barr virus and suspected to play
a role in the development of cancer,” says Lori Frappier, professor in
medical genetics and microbiology at U of T and senior author of a paper
in the April 1 issue of Molecular Cell.

“This research shows how EBNA1 interferes with natural cell growth
regulation by binding to a particular protein in cells, causing them to
continue growing and therefore increasing the risk of becoming
cancerous.”

Frappier explains that all cells contain the two proteins – p53 and USP7
– that work together to regulate cell growth. P53 is an important protein
whose level in the cell determines whether cells will continue to
proliferate or stop dividing and die. USP7 is a protein that binds to p53
and makes it stable. Under those conditions, cells stop growing and die,
which is a natural state of cell regulation. Once EBNA1 is introduced to
cells, however, this protein interferes with natural cell regulation by
binding to USP7 and preventing its interaction with the p53 protein.

“Normally, p53 levels will increase in response to certain problems in
the cell such as damaged DNA and this stops the cell from proliferating.
Through binding USP7, EBNA1 keeps the p53 levels low so cells will
continue to divide when they shouldn’t, which means they’re now more
likely to develop into cancer,” Frappier says.

“All viruses known to be able to cause cancer, like the human
papillomavirus that causes cervical cancer for example, have been shown
to work through this p53 protein, but up until now, no one’s ever found
any regulation of p53 that’s associated with the Epstein-Barr virus. That
was surprising because all other viruses that stimulate cell
proliferation do it through p53. The question was why this one didn’t.
What our research shows is that EBNA1 does actually impact on the p53
protein; it just does it in a different way than other viruses do.”

Frappier, a Canada Research Chair in Molecular Virology, also conducted
this research with Professor Aled Edwards, also of medical genetics and
microbiology at U of T, and Professor Cheryl Arrowsmith, of medical
biophysics at U of T and the Ontario Cancer Institute. Both Edwards and
Arrowsmith are also from U of T’s Banting and Best Department of Medical
Research and the Structural Genomics Consortium.

The researchers tested the effects of EBNA1 on human cells grown in
culture. Frappier says the paper provides a structural explanation of
this protein complex so scientists can see in molecular detail how the
EBNA1 protein binds to USP7 and the resulting impact on cell growth. Once
that level of detail is achieved, she says scientists can then design
specific mutations in these proteins to see what happens to cells when
the proteins don’t interact with one another. A better understanding of
these molecular mechanisms will hopefully lead scientists and researchers
to developing better methods of combating viruses like these which cause
disease, says Frappier.

Funding for the study was provided by the Canadian Cancer Society through
the National Cancer Institute of Canada and the Natural Sciences and
Engineering Research Council of Canada.

http://www.news.utoronto.ca/bin6/050331-1173.asp

Abnormal immune response to Epstein-Barr virus infection and evidence of
toxic events on a cellular level

The Epstein-Barr virus (EBV) causes infectious mononucleosis and has been
linked to two forms of cancer, Burkitt's lymphoma and nasopharyngeal
carcinoma. More recently, it has been suspected as the causative agent in
Chronic Fatigue Syndrome, a mysterious and rapidly proliferating disease
state. The EBV has the specific characteristic of attacking and damaging
thecells of the immune system.

Using the highly sophisticated micro-PIXE (particle induced X-ray
emission) technique, which is capable of investigation directly within
cells, a research team at Uppsala University in Sweden has been studying
the EBV and the effect of intracellular mercury. Their initial findings
were reported at
the Inernational Congress for Infectious Diseases. Rio de Janeiro,
Brazil. April 17-21, 1988. The authors work at the Department of
Infectious Diseases and Department of Radiation Sciences, Uppsala
University, Sweden, and Department of Virology, National Bacteriological
Laboratory, Stockholm, Sweden.

ABSTRACT:

Chronic illness in association with serological evidence of persistent
active Epstein-Barr virus (EBV) has been observed by several
investigators in recent years. The role of the virus as a causative agent
has not yet been determined. We have investigated 27 patients with
chronic malaise and 27
healthy controls. In addition to EBV serological testing we have analyzed
individual blood cells for the content of heavy metals, using a nuclear
micro-probe, in order to assess possible environmental exposure of
importance to immune functions.

Methods: An EBV serology panel,using indirect immunofluorescence, was
employed for concurrent measurements of all serum samples at a single
laboratory. Red and white blood cells from venous blood samples were
separated and prepared according to techniques described elsewhere. The
measurements of elemental concentrations in 20 red and 20 white blood
cells were performed in the Studsvik Nuclear Micro-probe at the Studsvik
Science Research Laboratory. This method, particle induced X-ray emission
for small targets (micro-PIXE) has been in routine use for research
purposes since 1983.

Results: The investigated group of patients displayed a significant
increase of EBV antibody titers as compared to controls. The
discriminative power could be increased by using a scoring technique in
each case. In the micro-PIXE determinations 80% of the patients had
detectable amounts of mercury in one or more of the cells measured as
compared to none in the control group. The detection limit was 0.5 ug/g
dry substance.

Conclusion: Our serological results compare well to findings presented by
other investigators in the field of chronic active EBV infections. In
addition, an abnormal presence of mercury in blood cells was noted.
Mercury, a heavy metal with known toxic properties in even minute
quantities, has immuno-modulatory effects in mammals. Our finding of
intracellular mercury in cases with apparent evidence of an immuno-regulatory
dysfunction warrants further elucidation.

BIO-PROBE COMMENT:These dramatic findings should have a vital impact on
the consideration of chronic exposure to low levels of mercury, as occurs
in subjects with mercury/silver amalgam fillings. Further evidence of the
findings of open-minded, competant researchers at reputable institutions
can be found in another recently published study. The researchers are
from the renowned Karolinska Institute in Stockholm, Sweden and the
University of Southern California School of Dentistry.

http://www.upi.com/NewsTrack/view.php?StoryID=20060120-050733-7661r

-- Epstein-Barr virus detected in breast cancer tissue and tumor cells may
impact the efficiency of chemotherapy drugs, French and Japanese researchers
say.

The virus, a member of the common herpesvirus family, has been previously
linked to skin and gastric cancer, as well as cancer of the salivary glands
and thymus. New studies have detected EBV in breast cancer specimens and
have prompted researchers to examine the
effect of infection with EBV on anticancer drug treatment. EBV genome
was identified in about half the biopsy specimens of breast cancer tissue
and tumor cell, however the viral load was highly variable from tumor to
tumor. These findings indicate that although EBV isn't likely to cause
breast cancer, it may contribute to tumor progression, the researchers said.

"Consequently, even if a small number of breast cancer cells are EBV
infected, the impact of EBV infection on the efficiency of anticancer
treatment might be of importance," said the researchers. The findings
were published in the January issue of the Journal of Virology.

Acta Dermato-Venereologica

Document Request Title: Gianotti-Crosti Syndrome and Allergic Background
Author(s): GIAMPAOLO RICCI ; ANNALISA PATRIZI ; IRIA NERI ; FERNANDO
SPECCHIA ; GIULIO TOSTI ; MASSIMO MASI
Source: Acta Dermato-Venereologica Volume: 83 Number: 3 Page: 202 -- 205
Publisher:Taylor & Francis Health Sciences
Abstract: The aim of the study was to verify whether there is a relationship
between Gianotti-Crosti syndrome and an allergic background in children.
Twenty-nine children affected by Gianotti-Crosti syndrome were first
screened for a large panel of microbiological examinations, including
serological and cultural tests for viruses and bacteria. A causative agent
was identified in only 10 cases (34.4%). In five cases a diagnosis of
Epstein--Barr virus infection was made on the basis of significant titres of
anti-Epstein-Barr virus antibodies (IgM) associated with constitutional
symptoms (fever, pharyngitis-tonsillitis). Our data concur with several
clinical studies demonstrating that Epstein-Barr virus is now the most
common viral agent associated with Gianotti-Crosti syndrome. For allergic
evaluation, a group of 59 age- and sex-matched children investigated for
recurrent infections were used as controls. The presence of atopic
dermatitis (24.1%) in those with Gianotti-Crosti syndrome was significantly
higher (p<0.005) than in the control group (6.8%). In addition, a more
common family history for atopy was 51.7% vs. 31% (p<0.027) and the
percentage of patients with total IgE greater than +2 SD for age higher than
in controls (27.6% vs. 13.7%), as was the percentage of specific IgE present
(31% vs. 17.2%). These results indicate that atopy is significantly
associated with Gianotti-Crosti syndrome.

The requested document is freely available only to registered users with an
online subscription to Acta Dermato-Venereologica